Although biologic agents have emerged as the preferred strategy for moderate-to-severe psoriasis, sparing around injection sites may be an underreported effect and represent inadequate systemic efficacy with fair local response of biologic treatment for psoriasis. Herein, we report six cases of extensive psoriasis presenting injection site sparing at biologics administration sites.

Keywords: Biologics, psoriasis, sparing effect

How to cite this article:Tsai YC, Tsai TF. Sparing of injection sites in patients with extensive psoriasis treated with various biologics. Dermatol Sin 2019;37:90-2

Biologic agents have emerged as the preferred treatment for moderate-to-severe plaque psoriasis, but their effectiveness in erythrodermic psoriasis (EP) has only been demonstrated in small case series with typically lower drug survival.[1],[2],[3] A recent case report showed sparing of adalimumab injection sites as a sign of secondary failure in a case of EP.[4] However, this phenomenon may be underreported and may occur in patients with primary biologics failure and in patients without EP in various biologics. We reported six cases who showed sparing of injection sites at our clinic [Table 1] and [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d.

Table 1: Characteristics of six patients with injection site sparing after subcutaneous biologics administration

A 39-year-old male with a 22-year history of psoriasis vulgaris was ever treated with narrow-band ultraviolet light B, methotrexate, efalizumab, cyclosporine with limited efficacy, and neotigason with adverse effects of hyperlipidemia. In December 2009, he started to receive etanercept 25 mg twice weekly. The psoriasis area and severity index (PASI) improved from 35.6 to 19.9 during weeks 0–33. Then, in August 2011, he received secukinumab with PASI = 40.2 and body surface area (BSA) = 85%. After 4 weekly injections, sparing areas around injection sites were observed on the abdomen (PASI = 26 and BSA = 70.5%) [Figure 1]a.

Details of five other patients including basic demographics, disease severity, event drugs, onset time after treatment, and previous biologics using histories are listed in [Table 1].

Discussion

The rarity of reports regarding sparing of injection sites may be due to the avoidance of injecting biologics into psoriatic lesions and because most patients responded so well that all lesions resolved at the same time. In fact, all patients in this case series started with extensive body surface involvement, making injecting into nonlesional skin impossible, and all patients showed an inadequate response to the biologics treatment. The spared lesions then became the only sites suitable for subsequent injections.

Intralesional therapy, including biologics, has been used in psoriasis treatment.[5] Despite a lack of direct evidence, it is conceivable that drug concentration is highest near the injection sites of biologic agents, at least for a short period of time and that the local effects may be longer lasting than expected.

The combination of prolonged local drug retention, poor drug redistribution, and inadequate systemic drug concentration may all theoretically contribute to the sparing phenomenon to produce an intralesional injection-like effect. Intralesional injection sites serve as a reservoir to maintain a longer duration of local action. Although this depot effect is more pronounced with lipophilic medications, water-soluble medications, such as methotrexate and even etanercept, have also been used locally.[6],[7]

It seemed that the injection site sparing phenomenon was not confined to any particular class of targeting points of monoclonal antibodies, because we observed this effect in both antitumor necrosis factor-alpha and anti-IL-17A drugs [Table 1]. However, injection frequency may play a role because we have not yet observed the same phenomenon after ustekinumab injections, given every 12 weeks, even though ustekinumab is the most commonly prescribed biologics for psoriasis. Repeated injections into the same area at reasonable time intervals may be needed to produce this sparing phenomenon.

A patient (Case 1) showed injection site sparing only with secukinumab injections, but not with previous efalizumab or etanercept. Although his response to secukinumab was only suboptimal, this response was better than with other previous systemic treatments. Thus, inadequate systemic drug concentration may also play a role. Although prior studies have shown the need of a higher drug dose in heavier patients, we suspect that a higher dose of biologics may also benefit patients with extensive or EP, considering the number of inflammatory cells and cytokines in such patients.

Sparing effects occurred in two patients (Cases 5 and 6) when PASI scores decreased slightly after the initiation of adalimumab treatment [Table 1]. Following further improvements of PASI under regular adalimumab treatment, the sparing effects disappeared. In contrast, injection site sparing occurred at the secondary failure of adalimumab treatment in Case 2. These three patients had previously been treated with etanercept with poor responses and no sparing phenomenon.

Conclusion

We observed an injection site sparing effect in (sub) erythrodermic and extensive psoriasis after biologics therapy. The exact mechanisms underlying this phenomenon remain to be elucidated.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

Dr. Ya-Chu Tsai has received speaker fees from Janssen-Cilag, Novartis, and Pfizer. Dr. Tsen-Fang Tsai has served as a consultant, paid speaker and participated in clinical trials including AbbVie, Boehringer-Ingelheim, Celgene, Eli Lilly, Janssen-Cilag, Leo Pharma, Galderma, Merck-Serono, Novartis, and Pfizer. The above companies have products for psoriasis treatment.